Metabolomics is the systematic study of all the metabolites present within a biological system, which consists of a mass of molecules, having a variety of physical and chemical properties and ...existing over an extensive dynamic range in biological samples. Diverse analytical techniques are needed to achieve higher coverage of metabolites. The application of mass spectrometry (MS) in metabolomics has increased exponentially since the discovery and development of electrospray ionization and matrix-assisted laser desorption ionization techniques. Significant advances have also occurred in separation-based MS techniques (gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, capillary electrophoresis-mass spectrometry, and ion mobility-mass spectrometry), as well as separation-free MS techniques (direct infusion-mass spectrometry, matrix-assisted laser desorption ionization-mass spectrometry, mass spectrometry imaging, and direct analysis in real time mass spectrometry) in the past decades. This review presents a brief overview of the recent advanced MS techniques and their latest applications in metabolomics. The software/websites for MS result analyses are also reviewed.
Metabolomics is the systematic study of all the metabolites present within a biological system, supply functional information and has received extensive attention in the field of life sciences.
•Mitochondrial quality surveillance is regulated by a variety of adaptive responses.•Mitochondrial fission favors the elimination of depolarized mitochondria through mitophagy.•The double-edge sword ...of mitophagy needs to be taken into consideration in the conception of new pharmacological approaches to treat MI.•Mitochondrial biogenesis represents a regenerative program to replace old and damaged mitochondria with new and healthy ones.•Mitochondrial bioenergetics is regulated by a metabolic switch between glucose and fatty acid usage, depending on oxygen availability.
Myocardial infarction (MI) is the irreversible death of cardiomyocyte secondary to prolonged lack of oxygen or fresh blood supply. Historically considered as merely cardiomyocyte powerhouse that manufactures ATP and other metabolites, mitochondrion is recently being identified as a signal regulator that is implicated in the crosstalk and signal integration of cardiomyocyte contraction, metabolism, inflammation, and death. Mitochondria quality surveillance is an integrated network system modifying mitochondrial structure and function through the coordination of various processes including mitochondrial fission, fusion, biogenesis, bioenergetics, proteostasis, and degradation via mitophagy. Mitochondrial fission favors the elimination of depolarized mitochondria through mitophagy, whereas mitochondrial fusion preserves the mitochondrial network upon stress through integration of two or more small mitochondria into an interconnected phenotype. Mitochondrial biogenesis represents a regenerative program to replace old and damaged mitochondria with new and healthy ones. Mitochondrial bioenergetics is regulated by a metabolic switch between glucose and fatty acid usage, depending on oxygen availability. To maintain the diversity and function of mitochondrial proteins, a specialized protein quality control machinery regulates protein dynamics and function through the activity of chaperones and proteases, and induction of the mitochondrial unfolded protein response. In this review, we provide an overview of the molecular mechanisms governing mitochondrial quality surveillance and highlight the most recent preclinical and clinical therapeutic approaches to restore mitochondrial fitness during both MI and post-MI heart failure.
Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the ...underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.
Obesity poses a severe threat to human health, including the increased prevalence of hypertension, insulin resistance, diabetes mellitus, cancer, inflammation, sleep apnoea and other chronic ...diseases. Current therapies focus mainly on suppressing caloric intake, but the efficacy of this approach remains poor. A better understanding of the pathophysiology of obesity will be essential for the management of obesity and its complications. Knowledge gained over the past three decades regarding the aetiological mechanisms underpinning obesity has provided a framework that emphasizes energy imbalance and neurohormonal dysregulation, which are tightly regulated by autophagy. Accordingly, there is an emerging interest in the role of autophagy, a conserved homeostatic process for cellular quality control through the disposal and recycling of cellular components, in the maintenance of cellular homeostasis and organ function by selectively ridding cells of potentially toxic proteins, lipids and organelles. Indeed, defects in autophagy homeostasis are implicated in metabolic disorders, including obesity, insulin resistance, diabetes mellitus and atherosclerosis. In this Review, the alterations in autophagy that occur in response to nutrient stress, and how these changes alter the course of obesogenesis and obesity-related complications, are discussed. The potential of pharmacological modulation of autophagy for the management of obesity is also addressed.
The present study was conducted to investigate the effects of high dietary lipid levels on growth, metabolism, antioxidant capacity, and immune responses of largemouth bass. Fish (initial body weight ...13.38 ± 0.11 g) were fed three isonitrogenous semi-purified diets containing 5%, 10%, and 20% lipid, respectively. The results indicated that fish fed 10% lipid diet showed significantly better final body weight, specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) compared with that fed 5% lipid diet. Meanwhile, fish fed 20% lipid diet had a significantly higher viscera ratio (VR), hepatosomatic index (HSI), intraperitoneal fat ratio (IPF), and liver lipid content than those fed the other diets. Higher alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) contents, and LDL-C/HDL-C value in plasma were recorded in fish fed 20% lipid diet, while higher insulin contents were obtained in fish fed 5% lipid diet. In addition, the highest carnitine palmitoyltransferase I (CPT1), AMP-activated protein kinase (AMPK), fructose-1,6-bisphosphatase (FBPase), and phosphoenolpyruvate carboxykinase (PEPCK) activities in the liver were also observed in fish fed 20% lipid diet. However, fish fed 20% lipid diet had a significantly lower superoxide dismutase (SOD) and catalase (CAT) activities and higher MDA contents in liver than those fed the other diets. The higher nitric oxide (NO) contents and inducible nitric oxide synthase (iNOS) activity in liver were recorded in fish fed 10% lipid diet. Moreover, the alkaline phosphatase (ALP), inducible nitric oxide synthase (iNOS) and lysozyme activities, and nitric oxide (NO) contents in plasma were higher in fish fed the 10% diets than the other groups. In conclusion, high dietary lipid levels could suppress growth performance and liver anti-oxidative capacity, and reduce immune responses of largemouth bass
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Background and Purpose
The growing epidemic of obesity and metabolic diseases necessitates the development of novel strategies to prevent and treat such diseases. Current research suggests that ...browning of white adipose tissue (WAT) promotes energy expenditure to counter obesity. Recent research suggests that activation of the TRPV1 channels counters obesity. However, the mechanism by which activation of TRPV1 channels counters obesity still remains unclear.
Experimental Approach
We evaluated the effect of dietary capsaicin to induce a browning program in WAT by activating TRPV1 channels to prevent diet‐induced obesity using wild‐type and TRPV1−/− mouse models. We performed experiments using preadipocytes and fat pads from these mice.
Key Results
Capsaicin stimulated the expression of brown fat‐specific thermogenic uncoupling protein‐1 and bone morphogenetic protein‐8b in WAT. Capsaicin triggered browning of WAT by promoting sirtuin‐1 expression and activity via TRPV1 channel‐dependent elevation of intracellular Ca2+ and phosphorylation of Ca2+/calmodulin‐activated protein kinase II and AMP‐activated kinase. Capsaicin increased the expression of PPARγ 1 coactivator α and enhanced metabolic and ambulatory activity. Further, capsaicin stimulated sirtuin‐1‐dependent deacetylation of PPARγ and the transcription factor PRDM‐16 and facilitated PPARγ–PRDM‐16 interaction to induce browning of WAT. Dietary capsaicin did not protect TRPV1−/− mice from obesity.
Conclusions and Interpretations
Our results show for the first time that activation of TRPV1 channels by dietary capsaicin triggers browning of WAT to counteract obesity. Our results suggest that activation of TRPV1 channels is a promising strategy to counter obesity.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes a heavy burden on the healthcare system ...globally. Current therapeutics to interfere with the underlying disease process in AD is still under development. Although many efforts have centered on the toxic forms of Aβ to effectively tackle AD, considering the unsatisfactory results so far it is vital to examine other targets and therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers to the build-up of unfolded or misfolded proteins within the ER, thus, perturbing the ER and cellular homeostasis. Emerging evidence indicates that ER stress contributes to the onset and development of AD. A thorough elucidation of ER stress machinery in AD pathology may help to open up new therapeutic avenues in the management of this devastating condition to relieve the cognitive dementia symptoms. Herein, we aim at deciphering the unique role of ER stress in AD pathogenesis, reviewing key findings, and existing controversy in an attempt to summarize plausible therapeutic interventions in the management of AD pathophysiology.
Searching for the highly active, stable, and high-efficiency bifunctional electrocatalysts for overall water splitting, e.g., for both oxygen evolution (OER) and hydrogen evolution (HER), is ...paramount in terms of bringing future renewable energy systems and energy conversion processes to reality. Herein, three-dimensional (3D) Ni3FeN nanoparticles/reduced graphene oxide (r-GO) aerogel electrocatalysts were fabricated using precursors of (Ni,Fe)/r-GO alginate hydrogels through an ion-exchange process, followed by a convenient one-step nitrogenization treatment in NH3 at 700 °C. The resultant materials exhibited excellent electrocatalytic performance for OER and HER in alkaline media, with only small overpotentials of 270 and 94 mV at a current density of 10 mA cm–2, respectively. The good performance was attributed to abundant active sites and high electrical conductivity of the bimetallic nitrides and efficient mass transport of the 3D r-GO aerogel framework. Furthermore, an alkaline electrolyzer was set up using Ni3FeN/r-GO as both the cathode and the anode, which achieved a 10 mA cm–2 current density at 1.60 V with durability of 100 h for overall water splitting. Density functional theory calculations support that Ni3FeN (111)/r-GO is more favorable for overall water splitting since the surface electronic structure of Ni3FeN is tuned by transferring electrons from Ni3FeN cluster to the r-GO through interaction of two metal species. Thus, the currently developed Ni3FeN/r-GO with superior water-splitting performance may potentially serve as a material for use in industrial alkaline water electrolyzers.
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